发现小分子p300抑制剂来源于新开发的以英达佐为中心的DNA编码图书馆
Yanrui Suo1,2, Kaige Li3, Xing Ling1,2
1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
Bioconjugate chemistry
|August 8, 2024
概括
我们开发了一种用于DNA编码库 (DEL) 构建的光促进反应,有效地创建一个英达佐核. 这种方法确定了针对E1A结合蛋白 (p300) 的新配体,为药物发现提供了一种新的方法.
科学领域:
- 化学生物学 化学生物学
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
背景情况:
- DNA编码图书馆 (DEL) 是药物发现的强大工具.
- 开发高效且兼容的反应对于DEL构造至关重要.
- 印达龙支架是药物化学中一个相关的核心结构.
研究的目的:
- 开发一种与DNA相容的,用于DEL合成的光促进反应.
- 根据英达龙支架构建一个DEL.
- 通过使用开发的DEL.来识别针对E1A结合蛋白 (p300) 的新型配体.
主要方法:
- 开发一种新的DNA兼容的光促进反应.
- 构建一个DNA编码的图书馆,其中包含一个因达佐核.
- 选DEL以识别E1A结合蛋白的结合物 (p300).
主要成果:
- 建立了一个高效且与板相容的光促进反应,用于因达佐支架的形成.
- 一个带有印达佐隆核心的DEL库已成功合成.
- 从DEL选择中确定了一系列针对p300的新联体.
结论:
- 在DNA编码库合成中,光促进反应是可行的.
- 开发的方法允许高效的DEL构造和目标识别.
- 这种方法为开发用于治疗应用的p300抑制剂提供了新的途径.
相关概念视频
Drug Discovery: Overview
10.4K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
10.4K
Inhibitors of Bacterial DNA Synthesis
130
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
130
Inhibitors of Viral Protein Synthesis
58
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
58


